INTRODUCTION — Endoscopic ultrasound (EUS) is a combination of endoscopy and ultrasonography. EUS can be used to visualize and sample mass lesions of the pancreas, gastrointestinal (GI) tract, posterior mediastinum, and retroperitoneum.
EUS has evolved from a diagnostic imaging modality to one that can also be used for invasive diagnostic and therapeutic procedures. These advances are largely due to the ability of EUS instruments to track a needle across an imaging plane into a target lesion. An important advantage of EUS is its ability to guide a needle to sample lesions that are too small to be identified by computed tomography (CT) or magnetic resonance imaging (MRI) or that are too well encased by surrounding vascular structures to allow for a percutaneous approach.
This topic will review the technique, indications, contraindications, and adverse events related to EUS-guided fine needle aspiration (EUS-FNA) in the GI tract. A discussion on indications and technique for EUS-guided fine needle (core) biopsy (EUS-FNB) is presented separately. (See "Endoscopic ultrasound-guided fine needle biopsy in the gastrointestinal tract".)
EUS-guided sampling of lesions in the mediastinum is discussed separately. (See "Endoscopic ultrasound-guided sampling of the mediastinum: Technique, indications, contraindications, and complications".)
TERMINOLOGY — Endoscopic ultrasound (EUS)-guided tissue acquisition can be performed with the following methods [1]:
●EUS-guided fine needle aspiration – EUS-guided fine needle aspiration (EUS-FNA) refers to EUS-guided puncture of a lesion followed by aspiration of cells or fluid for fluid analysis (eg, tumor markers, fluid chemistries, molecular markers), cytology, or histology.
●EUS-guided fine needle biopsy – EUS-guided fine needle biopsy (EUS-FNB) refers to EUS-guided core biopsy of a lesion to obtain tissue for histology.
PROCEDURE
Patient preparation — The preprocedure preparation for patients is similar to that described for patients undergoing upper gastrointestinal (GI) endoscopy (see "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Patient preparation'):
●Adjusting medications – Most patients do not need to discontinue aspirin or nonsteroidal anti-inflammatories when undergoing endoscopic ultrasound (EUS)-guided sampling. However, for most patients on anticoagulants and/or nonaspirin antiplatelet agents who undergo EUS-guided fine needle aspiration (EUS-FNA), the procedure-related bleeding risk is high (table 1). The management of antiplatelet and anticoagulant therapy in those undergoing endoscopy is typically individualized, managed in conjunction with the prescribing subspecialist, and is discussed separately. (See "Management of antiplatelet agents in patients undergoing endoscopic procedures" and "Management of anticoagulants in patients undergoing endoscopic procedures" and "Gastrointestinal endoscopy in patients with disorders of hemostasis".)
●Antibiotic prophylaxis – Most patients do not need prophylactic antibiotics prior to sampling solid lesions of the GI tract, while some patients with cystic lesions require preprocedure antibiotics (eg, patients with mediastinal cysts). The indications for antibiotic prophylaxis are discussed in more detail separately. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic ultrasound'.)
Equipment
Echoendoscope — EUS is performed with an echoendoscope (an endoscope with an ultrasound transducer engineered into its tip). The echoendoscope is a flexible instrument that has biopsy channels and can obtain reliable images at a depth ranging from 3 to 80 mm from the transducer. Two types of echoendoscopes exist, radial and curvilinear:
●The radial echoendoscope provides a 360-degree ultrasound image of the GI tract and surrounding structures. It is purely a diagnostic tool and does not allow for FNA or FNB. The radial EUS scope readily images lesions such as submucosal lesions of the esophagus, stomach, or duodenum as the layers of the esophagus, stomach, or duodenum are clearly seen. This scope provides a familiar cross-sectional view such as that seen with CT.
●The curvilinear array echoendoscope provides a 180-degree view that is in the same plane as the shaft of the echoendoscope, thereby permitting real-time visualization of the fine needle as it is advanced. This instrument has an electronic ultrasound array that scans in the long axis of the endoscope, in line with the viewing and biopsy channels. As a result, a needle advanced through the biopsy channel into the tissue of interest is in the plane of the ultrasound and thus visible in the ultrasound image in real time as an aspiration or biopsy is performed (image 1).
Color flow and Doppler features of the curvilinear echoendoscope also permit identification of vascular, ductular (such as biliary and pancreatic ducts), and cystic structures, which is important prior to FNA to avoid intervening blood vessels in the path of the aspiration needle.
Fine aspiration needles — Several needles are available for performing EUS-FNA, and each needle uses a catheter assembly with an attached handle mechanism that secures to the biopsy channel's Luer lock adapter on the echoendoscope. Needles range in size from 19- to 25-gauge, with a depth of penetration of up to 10 cm. Most needles have a central stylet beveled to match the needle tip, thereby enhancing the sharpness of the device.
Selecting a specific needle size depends on the target lesion type, lesion location, lesion size, and endoscopist preference [2,3] . For example, the 19-gauge needle is stiffer than a smaller (eg, 25-gauge) needle, and it may be difficult to manipulate in the duodenum with a sharply curved instrument. Smaller needles may be more easily directed and inserted into target lesions than larger needles.
Technique — The technical procedure of EUS-FNA of the GI tract includes selecting a site, advancing the needle, aspirating the sample, and preparing the specimen:
●Selecting a site for FNA – Selecting a site for FNA includes:
•Identifying a target lesion that will provide the most accurate disease stage if malignancy is suspected (image 2). (See "Clinical manifestations, diagnosis, and staging of esophageal cancer".)
•Examining the target location with Doppler imaging to avoid blood vessels and other structures that may be located between the tip of the echoendoscope containing the needle and the target lesion.
●Advancing the needle catheter apparatus – After a target lesion without intervening blood vessels has been identified, the needle catheter apparatus (containing a needle that is retracted into the sheath) is advanced through the working channel of the curvilinear echoendoscope with the endoscope's elevator in the down position. The needle apparatus is advanced into the endoscope until the device meets the insertion site of the biopsy channel's Luer lock adapter, and then the apparatus is secured in place.
Some degree of balloon insufflation at the tip of the echoendoscope may be necessary to allow acoustic coupling. To prevent puncturing the balloon with the needle tip, luminal pressure can be applied with the up/down dial of the echoendoscope.
●Obtaining the specimen – Under direct ultrasound guidance, the needle is directed through the wall of the GI organ nearest to the target lesion (eg, stomach, duodenum) and then into the lesion. A swift jabbing motion is occasionally necessary to traverse the muscularis propria and enter the lesion. When the needle has entered the lesion of interest, the stylet is withdrawn, and a 10 or 20 mL syringe is attached to the needle apparatus. Aspiration is then performed by simultaneously moving the needle in a to-and-fro motion inside the target lesion and fanning the target lesion while applying negative pressure using the syringe [4]. After the sample is obtained (but prior to removing the needle), the negative pressure should be released (this should be done by releasing the syringe plunger while not forcing it back to its neutral position). Reduced negative pressure (ie, by 1 to 2 mL) or the use of smaller-gauge needles (ie, 25-gauge) may result in less bloody aspirates, particularly with vascular tumors or lymph nodes. The needle apparatus is then removed from the echoendoscope.
Some advanced endoscopists prefer to pull back the stylet only in order to create negative pressure, rather than using a syringe. If a specimen is not obtained using this method, the stylet is withdrawn, and a syringe is used to create suction. Conversely, if the aspirated sample is bloody during initial sampling using a syringe, further sampling may be performed without the negative pressure from the syringe.
●Preparing and assessing the specimen – To prepare the specimen after removing the needle apparatus, air is forced through the needle using the same syringe, which expels the aspirated sample. This may be done into a cytologic preservative or applied directly onto a glass slide.
For rapid on-site evaluation (ROSE), two direct smears are usually made from a single pass; one slide is fixed with 95 percent alcohol for cytologic analysis in the laboratory, while the other slide is air dried and stained [5]. After the material has been smeared onto the glass slides, a saline wash is performed through the needle, and the material is collected to be made into a cell block. The stylet is then wiped off to remove any remaining blood and the needle purged of any remaining fluid using air. The entire needle device can then be reassembled for additional passes into the lesion.
●Number of FNA passes – Multiple passes can be performed to enhance the diagnostic yield as well as for special staining, or for microbiology purposes (eg, for patients with suspected lymphoma who require flow cytometry testing of the specimen). The same procedure can be used to aspirate tissue for microbiologic analysis, except the aspirate is placed in a small amount of sterile saline.
If a cytotechnologist or cytopathologist is present during the procedure to examine the slides, they can indicate when a sufficient cellular sample has been obtained. If a cytotechnologist or cytopathologist is not present, three passes are taken through lymph nodes and five to six passes are taken through pancreatic masses to ensure adequate cellularity in >90 percent of cases [6,7].
The optimal number of aspirates that are needed for achieving diagnostic accuracy is uncertain [7,8]. As an example, in a study including 95 patients with a variety of lesions estimated that at least seven passes were required for pancreatic and other non-lymph node lesions, while five passes appeared to be sufficient for lymph nodes [8].
Postprocedure care — After the procedure, patients are recovered from sedation or anesthesia. A fever after the procedure is not typical and warrants further investigation, although bacteremia is rare. (See 'Adverse events' below.)
The equipment is cleaned per procedural protocol. (See "Preventing infection transmitted by gastrointestinal endoscopy", section on 'Overview of endoscope reprocessing'.)
INDICATIONS
Diagnostic role of FNA — Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is used to sample lesions within or adjacent to the gastrointestinal (GI) tract; peri-intestinal structures such as lymph nodes; and masses in the pancreas, liver, adrenal gland, and bile duct. It has also been used to sample mucosal and submucosal lesions in which prior endoscopic biopsies have been nondiagnostic. Less commonly, it is used to aspirate peritoneal and pleural fluid.
Limitations of EUS-FNA include availability of equipment and endoscopic expertise, and the rare occurrence of false-negative or false-positive results that may lead to unnecessary surgery and are mostly related to interpretation of cytologic material [9].
Lesion type
Pancreatic lesions
●Solid pancreatic lesions – The role of EUS in the diagnostic evaluation and staging of pancreatic masses is discussed separately. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer" and "Endoscopic ultrasound in the staging of exocrine pancreatic cancer".)
Pancreatic lesions that are suspicious for metastases can also be visualized and sampled with EUS [10].
●Pancreatic neuroendocrine tumors – EUS can identify pancreatic neuroendocrine tumors (NETs), and EUS-FNA can provide nonoperative diagnosis with reported sensitivity ranging from 68 to 87 percent and specificity ranging from 86 to 100 percent [11-13]. The diagnosis and staging of pancreatic NETs is discussed separately. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms".)
●Cystic pancreatic lesions – EUS-FNA of pancreatic and peripancreatic cysts permits fluid analysis, while also demonstrating imaging characteristics [14,15]. The cyst fluid obtained via EUS-FNA can be analyzed for cytology, tumor markers, and molecular markers (table 2), and this is discussed in more detail separately. (See "Pancreatic cystic neoplasms: Clinical manifestations, diagnosis, and management", section on 'EUS-FNA findings associated with specific cysts'.)
EUS features suggestive of specific cyst types (eg, serous cystic tumors, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms) are discussed separately. (See "Classification of pancreatic cysts" and "Pancreatic cystic neoplasms: Clinical manifestations, diagnosis, and management", section on 'EUS-FNA findings associated with specific cysts'.)
Peri-intestinal lymph nodes — EUS-FNA can provide sampling of peri-intestinal lymph nodes for patients with lymphadenopathy [16-19]. In a study including 183 lymph nodes that were sampled by EUS-FNA, the sensitivity and specificity of FNA were 98 and 100 percent, respectively [19]. In addition, EUS-FNA was more accurate compared with EUS evaluation alone (99 versus 75 percent). The role of EUS-FNA in sampling lymph nodes and staging for patients with esophageal cancer is presented separately. (See "Endoscopic ultrasound in esophageal cancer", section on 'Endoscopic ultrasound-guided fine-needle aspiration biopsy'.)
EUS-FNA has been useful for the diagnosis of other disorders associated with lymphadenopathy such as Hodgkin and non-Hodgkin lymphoma, particularly if flow cytometry is used [20,21]. Cytology can be used to diagnose large cell non-Hodgkin lymphoma, but is more limited in low-grade lesions [22]. For some patients with suspected lymphoma, samples may be obtained by using EUS-FNA initially and then by using EUS-guided fine needle biopsy (EUS-FNB) if onsite cytopathology suggests the need for core tissue. (See "Endoscopic ultrasound-guided fine needle biopsy in the gastrointestinal tract".)
Upper GI tract lesions — Esophageal or gastric wall thickening can be evaluated with EUS-FNA. As an example, in a study of EUS-FNA evaluation of 103 lesions arising from the GI wall (excluding stromal tumors), sensitivity varied with the type of lesion (eg, 89 percent for non-Hodgkin gastric lymphoma compared with 40 percent for gastric adenocarcinoma) [16]. (See "Approach to the patient with large gastric folds".)
EUS-guided detection and tissue acquisition of subepithelial lesions of the upper GI tract (eg, GI stromal tumors [GISTs]) is discussed separately. (See "Endoscopic ultrasound for the characterization of subepithelial lesions of the upper gastrointestinal tract" and "Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors".)
Lower GI tract lesions — Lower GI tract lesions such as suspected GIST or perirectal mass lesions can be evaluated with EUS-FNA. However, FNA is infrequently required for evaluating lesions in the lower GI tract [23]. (See "Endoscopic ultrasound for evaluating patients with rectal cancer" and "Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors", section on 'Diagnostic evaluation'.)
Other lesions — Other lesions that can be sampled using EUS-FNA include:
●Bile duct strictures and gallbladder masses – EUS-FNA has been used in the evaluation of bile duct strictures and gallbladder masses, and it is often performed in addition to endoscopic retrograde cholangiopancreatography (ERCP) and brush cytology [24,25]. However, for patients with suspected cholangiocarcinoma, EUS-FNA is reserved for patients who are not candidates for liver transplantation. EUS-FNA can rarely result in seeding of the biopsy tract with malignant cells, which may preclude an otherwise eligible transplantation candidate from undergoing liver transplantation. The diagnosis and staging of cholangiocarcinoma is discussed separately. (See "Clinical manifestations and diagnosis of cholangiocarcinoma".)
The diagnostic accuracy of EUS-FNA for biliary and gallbladder lesions has been evaluated in multiple studies [25-27]. In a meta-analysis of 20 studies including 957 patients, the sensitivity of EUS-FNA for detecting malignant biliary strictures was 80 percent, and specificity was 97 percent [27]. In another meta-analysis of nine studies including 284 patients with bile duct or gallbladder lesions, EUS-FNA was 84 percent sensitive and 100 percent specific for diagnosing bile duct and gallbladder cancers [26].
●Uncommon uses – Small case series and case reports have suggested that EUS-guided FNA may be useful for sampling solid liver lesions [16,28,29], adrenal lesions [30], or peritoneal fluid [31,32].
CONTRAINDICATIONS — There are few contraindications for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA); however, the most common contraindications are related to routine upper endoscopy and include:
●Patients who cannot tolerate moderate sedation, monitored anesthesia care (MAC), or general anesthesia. (See "Anesthesia for gastrointestinal endoscopy in adults".)
●Patients who are hemodynamically unstable.
●Patients with gastrointestinal (GI) obstruction (eg, duodenal stricture due to a lesion in the head of the pancreas) may undergo EUS, but the imaging is limited to an area proximal to the level of obstruction.
For patients with abnormal coagulation studies (platelet count ≤50,000/microL; international normalized ratio [INR] >1.5), EUS-FNA is relatively contraindicated. Management of anticoagulants and antiplatelet agents for patients undergoing endoscopic procedures is discussed in detail separately. (See "Management of anticoagulants in patients undergoing endoscopic procedures" and "Management of antiplatelet agents in patients undergoing endoscopic procedures".)
ADVERSE EVENTS — Endoscopic ultrasound (EUS) and EUS-guided sampling are generally safe procedures. Some complications are due to the effect of procedural sedation (eg, hypotension), while others are due to the endoscopy itself or the sampling procedure. In a pooled series of nearly 2500 patients who underwent EUS-guided fine needle aspiration (EUS-FNA), the overall rate of adverse events ranged from 0 to 3 percent, and complications mostly included infection, bleeding, and pancreatitis [33,34]. Mortality was very rare, with one death reported (0.04 percent).
However, a higher rate of adverse events was reported in a subsequent study that was limited to 502 patients who underwent lower gastrointestinal (GI) EUS-FNA [23]. Overall, adverse events developed in 103 patients (21 percent), and serious adverse events were seen in 28 patients (6 percent). The most commonly reported serious adverse events were pain (5 percent) and bleeding (0.6 percent), while risk factors for adverse events included preprocedure pain, malignant lesion, and lesion site other than lymph node or intestinal wall. In addition, EUS-FNA is infrequently required for evaluating lesions in the lower GI tract. (See 'Lower GI tract lesions' above.)
Endoscopy-related — Complications associated with EUS may be due to the upper GI endoscopy itself (without FNA) and/or the associated sedation and anesthesia (eg, hypotension) [35]. These complications are discussed in more detail separately. (See "Adverse events related to procedural sedation for gastrointestinal endoscopy in adults" and "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Complications'.)
FNA-related — Reported complications of FNA are generally rare and include [36]:
●Infection such as bacteremia (rare) [37-39]
●Bleeding (usually minor; hemorrhage requiring transfusion is rare)
●Needle tracking with malignant or infectious cells (rare) [40-47]
●Pancreatitis after sampling of solid or cystic pancreatic lesion (rare) [33,48]
SUMMARY AND RECOMMENDATIONS
●General principles – Endoscopic ultrasound (EUS) is a combination of endoscopy and ultrasonography. EUS can be used to visualize and sample lesions of the pancreas, gastrointestinal (GI) tract, posterior mediastinum, and retroperitoneum. EUS is an imaging modality that can be used diagnostically and for invasive diagnostic and therapeutic procedures. (See 'Introduction' above.)
EUS-guided tissue acquisition can be performed with the following methods (see 'Terminology' above):
•EUS-guided fine needle aspiration – EUS-guided fine needle aspiration (EUS-FNA) refers to EUS-guided puncture of a lesion followed by aspirating cells or fluid for fluid analysis, cytology, or histology.
•EUS-guided fine needle biopsy – EUS-guided fine needle biopsy (EUS-FNB) refers to EUS-guided core biopsy of a lesion to obtain tissue for histology.
●Procedure – EUS is performed with an echoendoscope (an endoscope with an ultrasound transducer in its tip). While radial EUS can provide diagnostic imaging, curvilinear EUS provides real-time ultrasonographic guidance for fine needle aspiration (EUS-FNA). The technical procedure of EUS-FNA of the GI tract includes selecting a site, advancing the needle, aspirating the sample, and processing the specimen. (See 'Technique' above.)
•Pre- and postprocedure care – Pre- and postprocedure care is similar to that for patients who undergo upper GI endoscopy. (See 'Procedure' above and "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)".)
•Clinical applications – EUS-FNA is used to sample lesions within or proximal to the GI tract; peri-intestinal structures such as lymph nodes; and masses in the pancreas, liver, adrenal gland, and bile duct. (See 'Indications' above.)
•Contraindications – There are few contraindications for EUS-guided sampling; however, the most common contraindications are related to upper endoscopy itself, including hemodynamic instability, inability to tolerate anesthesia/sedation, and GI obstruction. (See 'Contraindications' above.)
•Adverse events – EUS and EUS-guided sampling are generally safe procedures, and complications are infrequently reported. Some complications are due to the effect of procedural sedation (eg, hypotension), while others are due to the endoscopy itself or the sampling procedure (infection, bleeding, pancreatitis). (See 'Adverse events' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Ian D Norton, MBBS, PhD, who contributed to an earlier version of this topic review.
